7,39 The concepts of allostasis and allostatic load have been championed by McEwen to describe how chronic stress—”wear and tear”—can affect well-being through over-action of adrenal steroid secretion and the sympathetic nervous system.4,40 Oxytocin and vasopressin secretion are other SB216763 pathways with multiple effects on birth, lactation, bonding, mate selection, and aggression. There are gender differences in the sociotypic Inhibitors,research,lifescience,medical responses, with females tending to (de)fend and befriend and males to fight or flight.41 This has become the basis for the new discipline of social neuroscience. We believe, however, that one of the major pathways of influence on sociotypic development

during the human life cycle is through nutrition, and this is shown in Figure 2. Figure 2 The effects of nutrition on the sociotype during the life cycle. THE ROLE OF NUTRITION Inhibitors,research,lifescience,medical ON THE SOCIOTYPE DURING THE LIFE CYCLE Nutrition may be likened to the fuel that drives the body’s physical and psychological motor and should therefore be of the highest octane. From the research on the neonatal origins of adult disease (Barker hypothesis and metabolic programming)42 and longevity (telomere lengths43–45) it is now Inhibitors,research,lifescience,medical recognized that nutritional influences begin at minus nine months. Famine pregnancy studies

from Holland46 and China47 confirm the increase in schizophrenia in the adult progeny. Nutrition affects many stages: pregnancy, breast-feeding, and weaning. The concept of the bonding and the “good and bad breast” stresses the importance of parenting attitudes. Milk contains endocannabinoids which are crucial for infant suckling.48 The endocannabinoid Inhibitors,research,lifescience,medical neurotransmitter modulator system is derived from essential omega-6 polyunsaturated fatty acids necessary for the synthesis of 2 arachidonyl glycerol and regulates appetite in a quasi-feedback loop.49 In rodents, maternal grooming influences serotonin activity, steroid secretion, and the methylation and

Inhibitors,research,lifescience,medical acetylation status of gene expression.50 Adolescents are vulnerable to cultural influences concerning body image and to the development of eating disorders. In some people nutrition may affect their cognitive assessments (food and mood).51 Three of the principal 17-DMAG (Alvespimycin) HCl neurotransmitters—serotonin, norepinephrine, and dopamine—are derived from essential amino-acids tryptophan, phenylalanine, and tyrosine. It is possible that some of the abnormal cognitive functioning in anorexia is due a lack of such precursors, which can be alleviated by oral tyrosine supplementation (Israel, Avraham & Berry, unpublished data). Eating disorders are examples par excellence of culture-bound diseases of the sociotype (“nothing tastes as good as thinness feels”), as discussed elsewhere.1 Brain peptides—orexins—provide a link between eating behavior, body weight, and sleep.

Micro-structured biomaterial filaments were also

used in vitro and in vivo to induce the formation of Büngner bands and increase the gap between the stumps after peripheral nerve repair using tubulization. For this purpose, resorbable polycaprolactone (PCL) filaments were formed by a melting extrusion technique using capillary size molds and coated with poly-d-lysine and Selleckchem P450 inhibitor laminin (Ribeiro-Resende et al. 2009). Based on the information reported above, the present authors developed a strategy to increase the axonal regeneration process after using the tubulization technique, by combining the use of a tubular Inhibitors,research,lifescience,medical prosthesis made of PCL with a supraorganized collagen foam implant placed inside the tube, and the results were compared with the use of the autograft technique. Morphological and morphometrical analyses lead to the conclusion that the

above mentioned approach increased the Schwann cell reactivity, as seen Inhibitors,research,lifescience,medical by the S100 and p75NTR expressions. Also the myelin thickness and the “g” ratio data demonstrated a better reorganization of the regenerated nerves when subjected to the proposed experimental approach. Materials and Methods Preparation of collagen with supra-molecular organization The collagen samples were extracted from the calcaneal tendon of cattle using a patented technique (#P.I.97015709, B. C. Vidal). Fragments of bovine tendon Inhibitors,research,lifescience,medical samples were cleaned and immersed in a solution containing 5% acetic Inhibitors,research,lifescience,medical acid, 0.01% HCl, and 1 mg of pepsin/g of tendon, maintaining at 7–10°C for 24 hours. The dissolved collagen was filtered and the fibers reconstituted by adding a 5% NaCl solution. The fibers thus obtained were dialyzed against distilled water at 5°C in a 6-mm-diameter tube, exchanging the water every 24 hours. One and a half liters of water were needed to acquire a total of 200 g of collagen with a supra-molecular organization (Oliveira et al. 2005). This was accomplished examining the collagen gel after dialysis Inhibitors,research,lifescience,medical with polarized

light microscopy (PLM) to detect the reconstituted fibers birefringence. Furthermore, gel was extruded and the helical arrangement of collagen fibrils old was detected by their birefringence by PLM (see Vidal 1995). Construction of the prosthesis for tubulization The tubular prosthesis was made using the solvent technique, as previously described (Pierucci et al. 2008). The polymer solution was prepared by adding 1.65 g of PCL (molecular weight = 100 kDa; PURAC Biochem, Gorinchem, the Netherlands) to 33 mL of solvent (dichloroethane; Merck, Darmstadt, Germany). After initial solubilization, the solution was left at room temperature for 12 hours to complete the homogenization. The next day, the solution was placed on a plate contained in a glass vat of which the middle part was saturated with solvent.

Eating disorders consist of severe disturbances in eating behavior, and the spectrum encompasses anorexia nervosa, bulimia, and sleep-related eating disorder.60-66 Anorexia nervosa About 90% of anorexia nervosa occurs In females, and the prevalence of this

condition among women In late adolescence and early adulthood Is approximately 0.5% to 1.0%.13 Peak onset occurs bimodally at ages 14 and 18 years. Essential features Include refusal by the Individual to maintain a minimally normal body Inhibitors,research,lifescience,medical weight, Intense fear of gaining weight, and a significant disturbance In body perception (shape or size). Subsets Include restricting type (weight loss Is Induced by fasting, dieting, or vigorous and excessive exercise) and binge-eating/purging Inhibitors,research,lifescience,medical type. In anorexia nervosa Individuals, Insomnia together with other depressive symptoms, such as depressed mood, Irritability, and decreased libido, can also be present.7 Long-term mortality is over 10% due to starvation, suicide, or electrolyte Imbalance.7 Bulimia nervosa This eating disorder occurs in 1% to 3% of adolescent and young female adults, and Is characterized by binge-eating and Inappropriate compensatory methods to prevent weight gain. These behaviors must occur on the average at least twice a week for 3 months. Subsets Include the purging type (use of self-Induced

vomiting or misuse of laxatives, diuretics, or enemas during Inhibitors,research,lifescience,medical the current episode) or the nonpurging type In which

abnormal behaviors, such as fasting or excessive exercise, Inhibitors,research,lifescience,medical are utilized. Bulimic Individuals are usually within the normal weight range, although some are slightly Ki16425 datasheet underweight or overweight. Anxiety or depressive symptoms frequently occur. Sleepwalking has also been reported In bulimic Individuals. Nocturnal eating (drinking) syndrome Like sleepwalking, nocturnal eating/drinking syndrome represents Inhibitors,research,lifescience,medical a parasomnia. This sleep disorder Is characterized by recurrent awakenings with Inability to return to sleep without eating or drinking. This problem occurs primarily during Infancy and early childhood, with a prevalence Phosphoprotein phosphatase of 5% In children between ages 6 months to 3 years. Nighttime waking can become conditioned to hunger and eating. After consuming the expected amount of food or drink, return to sleep Is rapid. The prevalence In adults Is unknown, but appears more common In women. Manni et al reported 5.8% prevalence among 120 adult subjects (51 males, 69 females, mean age 42.6 years) referred for Insomnia complaints.60 Schenck et al described 19 adults with sleep-related eating (SRE), with mean age of onset of 24.7±9.1 years, and reported that psychiatric disorders affected 47.4% (9/19) of these patients; 31.6% (6/19) were diagnosed with affective disorders, while 21.0% (4/19) had anxiety disorders.61 WInkelman reported that 35% (8/23) of their patients with SRE had a lifetime eating disorder diagnosis.

Crook is supported by the Chief Scientific Officer of Scotland, The Leng Foundation, and The Anonymous Trust.
Malignant gliomas are among the most pernicious of human tumors and are characterized as regionally invasive, usually recurring within two centimeters of their origin after resection [1]. Although many advances in treatment have been made, they have yielded only modest survival

benefits [2]. Numerous Inhibitors,research,lifescience,medical chemotherapeutic drugs have demonstrated significant antitumor activity in preclinical studies, but often this effectiveness is not translated into clinical trials in humans. A major factor contributing to this is the limitation of systemic delivery, namely, the impermeability of the blood-brain barrier as well as dose-limiting toxicities of many compounds. This highlights the need for efficient, specific methods of delivery in the treatment of human GBM. The ideal delivery method would be one that achieves adequate Inhibitors,research,lifescience,medical coverage of the tumor volume while minimizing any unwanted toxicities. Optimal delivery requires three important components: the ability to target Inhibitors,research,lifescience,medical the tumor while minimizing local

and systemic effects, applicability over a wide range of therapies, and a safe, efficacious method of continuous delivery with noninvasive methods to monitor volumes of distribution (Vd) of agents. In this paper, we describe our experience with convection-enhanced delivery (CED) Inhibitors,research,lifescience,medical across these three domains and highlight the translational goals of this work. The ultimate goal is to safely bring such systems and therapies to human trials, and eventually, to optimize these methods in clinical practice and establish standards of care. 2. Convection-Enhanced Delivery Convection-enhanced delivery, pioneered by Bobo et al., delivers agents directly into the tumor and the surrounding Inhibitors,research,lifescience,medical parenchyma with continuous, positive-pressure infusion [3]. While other methods of delivery exist, such as through intraarterial and intrathecal routes, these are often limited by the blood-brain and blood-CSF

barrier as well as unwanted toxicities. Furthermore, compared to diffusion-based drug delivery (i.e., carmustine wafers), convective Montelukast Sodium delivery Abiraterone allows for larger volumes of distribution, as it is not limited by diffusive spread by concentration gradients [4]. Importantly, CED allows direct access to the tumor bed, achieving high local concentrations of drug with minimal systemic absorption. One of the first therapeutic agents given via CED for malignant gliomas in a clinical trial was diphtheria toxin conjugated to transferrin (TF-CRM107) [9]. This pioneering clinical trial highlighted the capability of CED to maximize therapeutic effect while limiting toxicity, as adverse events were limited.

The trauma teams were assisted by nurses and flight coordinators on duty in the Emergency Medical Dispatch center (EMD) situated in the Department of Emergency Medicine at UNN. Communication technology The VC system has two-way video and audio. Two cameras were P505-15 installed in the emergency room at LYB; one camera above the patient bed and one wall-mounted overview camera. Both cameras have pan, tilt and zoom. Physiological variables with trends (ECG, heart rate, blood pressure, oxygen blood saturation and temperature) can be viewed real

time at both locations. At UNN, the VC system was installed with one camera and two 37¨ wall-mounted widescreens in the conference center of the Inhibitors,research,lifescience,medical EMD. The primary design concept was to minimise the amount of technology interaction for the team working around the patient in the rural emergency room. The technology therefore can be remotely controlled from the EMD. For data compression and decompression of video Inhibitors,research,lifescience,medical streams we used two Tandberg video codecs (Tandberg, Lysaker, Norway), connected with a 2 MB/s data network. For comparison, we also tested virtual team building without the Inhibitors,research,lifescience,medical VC system, using conventional telephones for communication between hospitals. The available telephones were a mix of wall-plugged units, wireless handsets, and loud-speaking telephone conference units. Simulation trials

We tested the “virtual emergency team” in simulated emergency scenarios (Table ​(Table1).1). The patients were healthy volunteers,

instructed to play symptoms and signs, and given realistic appearance by professional make-up. Physiological variables were generated by simulators and displayed real time on monitors, Inhibitors,research,lifescience,medical at both locations during VC, and at LYB only during telephone scenarios. A facilitator (SRB) provided additional information, such as respiratory sounds and urine color, when participants asked for it. Participants had no former experience Inhibitors,research,lifescience,medical in using the VC system. They were given a 15 minutes introduction on how to use it followed by a practical training session (case A, Table ​Table1).1). The same team members at both hospitals cooperated on another two Tryptophan synthase scenarios (case B – E, Table ​Table1).1). Team 1 used videoconferencing for all scenarios while team 2 and 3 explored both communication modes. The teams were allowed to work 45 minutes on each case. Table 1 The scenarios in brief as presented for the three teams. Data collection and analysis An external observer (FL) followed each scenario, focusing on intra- and inter-group communication. Semi-structured group interviews were conducted following each of the nine simulated scenarios (case A – E, Table ​Table1).1). Group interviews facilitate interaction and exchange of ideas between the informants, and was chosen to allow team members to discuss their experience, behaviour, group dynamics and how the team could work better together.

Drugs that directly activate the reward system may produce learning that diverts the individual to those behaviors that repeat the drug-induced feelings of reward. An important feature of this form of neuroplasticity is that it is stable and perhaps permanent. The dopamine release caused by a drug of abuse tends to be greater than that of natural rewards, and to continue with repeated exposure rather

than diminish, as is the case with natural, expected rewards2. Thus, the drug experience becomes associated with environmental cues and acquires increasing salience. Individuals who develop this neuroplasticity tend to suffer from a chronic illness with potential for relapse, Inhibitors,research,lifescience,medical even years after the last dose of the drug. Drug-taking then acquires more salience than natural or adaptive behaviors. Evidence of the plasticity that has occurred with the development of addiction

can be demonstrated by brain Inhibitors,research,lifescience,medical imaging studies that show rapid activation (increased blood flow to reward pathways) when drug-related cues are shown to addicts who have been free of drugs for at least a month.3 Even cues so brief that they do not reach consciousness (33 msec) can produce rapid activation.4 During brain reward system activation, the addict reports drug craving. The strength of the craving Inhibitors,research,lifescience,medical is related directly to the amount of endogenous dopamine released in reward structures, as measured by displacement Inhibitors,research,lifescience,medical of labeled raclopride in positron emission tomography (PET) studies.5 More direct studies of the plasticity induced by drugs of addiction can be seen in animal models. Shaham and colleagues have studied the relapse or reinstatement of drug-taking in rats trained to self-administer intravenous cocaine.6 Availability of cocaine

is signaled by a light that the animal then associates with cocaine. After the behavior is well trained, the cocaine can be turned off; thus, pushing the lever no longer provides cocaine. After the extinction process is complete, the animal can be tested for reinstatement by returning it to the Inhibitors,research,lifescience,medical drug-taking environment and giving the light cue. This is considered to be a model of “relapse” in human addicts. The intensity of relapse can be measured Endonuclease by the number of times the light causes the rat to press the bar despite not receiving any cocaine. Eventually, the unrewarded bar pressing stops. It was found that reinstatement occurred when rats were tested 1 week after extinguishing cocaine-seeking, but the reinstatement was significantly greater at 4 weeks, and progressively increased further if the rats were allowed to rest in their cages for up to 6 months before relapse testing. The strengthening of relapse tendency over time has been called “incubation” and is associated with MAPK inhibitor increases in the levels of the growth factor brain-derived neurotrophic factor (BDNF) in the ventral tegmental area and in the nucleus accumbens.

These actions may serve to resolve the mental imperative of the intrusive thoughts by inducing the person to perform repeated actions or movements that often appear ritualistic. The ritual is composed of sets or sequences of these behaviors, often in order, and may consume much of the patient’s waking attention. OCD is not rare, and occurs with a lifetime prevalence of up to 3%.1 Even with medication as well as behavioral

modification, more than one in ten Afatinib order patients are significantly impaired in their activities of daily living.2 Obsessive-compulsive symptoms (OCS) may be seen in OCD itself, Inhibitors,research,lifescience,medical or may appear in other psychiatric conditions,. However, despite a number of case reports, no unifying theory of causation has been clearly established. Inhibitors,research,lifescience,medical An increased prevalence of OCS, however, has been noted in refractory epilepsy,3 particularly with temporal lobe epilepsy (TLE). There is therefore interest in whether these two conditions are causally linked. Epilepsy can affect up to 1% of the population, and is one of the commoner groups of neurological disorders in adults.4,5 This group of

disorders is defined as the clinical expression of repeated epileptic seizures occurring spontaneously (unprovoked). Inhibitors,research,lifescience,medical There may be many possible causes. These include genetic conditions with onset at various ages and stages of development, and a large spectrum of acquired insults such as conferred by trauma, strokes, neoplasia, inflammation, or infections. Most patients with frequent seizures are offered medical treatments, but even with a wide choice of antiepileptic drugs (AEDs), over one quarter of patients are refractory to medical treatment.

Patients with epilepsy may also express Inhibitors,research,lifescience,medical a number of patterns of behavioral abnormality and personality characteristics, and experience memory, emotional, behavioral, and social disabilities.6-9 Up to 40% of Inhibitors,research,lifescience,medical epilepsy patients may be so disabled, particularly in the patients with pharmacoresistant seizures.6 Ertekin and colleagues’ review10 notes that in refractory epilepsy, some 70% had psychiatric disorders7; prevalence of axis I psychiatric disorders ranged up to 80%8; and that using the Symptom Checklist-90- GBA3 Revised (SCL90-R), adults with partial epilepsy had a prevalence of 88% mental health complaints when scoring for symptoms in the index.9 In epilepsy, mood disorders, including depression and anxiety, are frequent.10 In over 200 patients, anxiety was found in almost 25%.11 As part of this behavioral disturbance, patients may present with features of OCD. This review will examine the links between OCD and epilepsy, and review the evolution of the literature on case reports, case series, and larger retrospective controlled studies. Included will be the components of OCD seen in epilepsy, effects of medical and surgical treatments, and an overview of the theoretical neurobiological underpinnings that might link the two disorders.

As these examples

show, autonomous 13C flux analysis—as any automation—entails the risk that raw data of insufficient quality are processed. Therefore, the implementation of routines SB202190 in vivo checking the quality of the original data, e.g. checking for detector overload and data of signals of insufficient intensity are crucial. In Flux-P, MDVs are removed from the analysis, if they cause improper flux ratios assuming a faulty MDV value of this particular fragment. However, equally possible is the use of incomplete or erroneous metabolic networks used for the flux ratio calculation. In order to prevent potentially Inhibitors,research,lifescience,medical wrong MDV exclusions and disclosing faulty networks, routines that check alternative network models have to be implemented. In summary, the automated analysis of 13C labeling data Inhibitors,research,lifescience,medical with Flux-P allows not only a fast pre-screening or initial analysis of large amounts of data but the fully automated calculation of high quality metabolic flux ratios and intracellular fluxes.

Observed differences from manually calculated flux distributions can be attributed to shortcomings of Inhibitors,research,lifescience,medical the analyzed data to unambiguously resolve all metabolic fluxes rather than to errors in the automated calculation. 3. Conclusions Existing software for 13C-based metabolic flux analysis—such as FiatFlux, OpenFLUX or 13CFLUX—supports experts in the complex analysis of intracellular fluxes, but requires several steps that have to be carried out manually, hence restricting their use for data interpretation to rather small numbers of experiments. Flux-P makes

it possible to automatically process 13C-based MFA of single as well as numerous input data sets. The interactive steps that are essential in the Inhibitors,research,lifescience,medical underlying software (FiatFlux in the current prototypical implementation) are replaced by specific scripts that emulate the user interaction, owing to the observation that the user acts, to a considerable extent, according to quantifiable criteria. In addition Inhibitors,research,lifescience,medical to the significant acceleration of the analysis process, Flux-P achieves a consistent analysis workflow and applies the same set of parameters to each data set, directly producing comparable all results. We showed that it is easy to integrate software as services via the jETI technology as soon as it can be operated in headless mode. The functions of the software are then available as platform-independent services and can be used for agile workflow definition within Bio-jETI. Encouraged by the good results that we have obtained with the prototypic implementation described in this paper, we are going to follow the approach further. Next to the implementation of data quality and model validity checks, discussed in section 2.8, we envisage the implementation of the analytic framework presented by Rantanen et al.

Clinical findings of sarcomere HCM are indistinguishable from those of Z-band HCM, and these two types of HCM show indistinguishable histopathologic features such as myocyte and myofibrillar disarrays, myocyte hypertrophy, and interstitial fibrosis. Table 1 Genetic diversity of idiopathic cardiomyopathy (ICM). There is another HCM-like disease, “glycogen-storage

HCM”, caused by mutations affecting mitochondrial and lysosomal function, including the mutations Inhibitors,research,lifescience,medical in the genes for γ-2-regulatory subunit of the AMP-activated protein kinase (PRKAG2), lysosome-associated membrane 2 (LAMP2), α-1,4-glycosidase (GAA) and α-galactosidase A (GLA) (5, 9). Among them, LAMP2, GAA, and GLA mutations were identified in the patients with Danon’s disease, Pompe disease, and Fabry’s disease, respectively. They were known as glycogen-storage metabolic disorders and affected not only cardiac Inhibitors,research,lifescience,medical muscle but also other organs (skeletal muscle in Danon’s disease, skeletal muscle and liver in Pompe disease, and skin, eye and kidney in Fabry’s disease). However, clinical examinations revealed that these diseases sometimes predominantly affecting the heart, usually manifested with massive LV hypertrophy and electrophysiologic abnormalities. Intracellular vacuoles selleck inhibitor containing glycogen

could be found in the hypertrophied hearts with these metabolic gene Inhibitors,research,lifescience,medical mutations and the pathological features of sarcomere/Z-band HCM, such as myofibrillar disarrays, were usually Inhibitors,research,lifescience,medical absent in the glycogen-strage HCM. In addition, the patients carrying LAMP2, GAA, and GLA mutations have family histories of the disease, which is consistent with autosomal recessive (LAMP2 and GAA mutations) or X-linked (GLA mutation) inheritance,

suggesting that deficiency of these enzymes are the direct cause of glycogen-storage HCM. As for the functional alteration due to the genetic abnormalities, Inhibitors,research,lifescience,medical it was reported that the MYH7 mutations, Arg403Gln or Leu908Val, affected the actin-myosin interaction (10), providing a hypothesis that the cardiac hypertrophy in HCM was compensation for decreased cardiac contraction due to the sarcomere abnormality. However, further functional analyses of HCM-associated mutations indicated that a common functional alteration caused by the mutations in various sarcomere genes is the increased Ca2+-sensitivity of muscle contraction, i.e., leftward shift of the pCa-tension relationship curve (11). The increased Ca2+-sensitivity implies that the cardiac muscle carrying the mutation can generate Parvulin force at a relatively low Ca2+-concentration where normal muscle should be relaxed, and this can well explain the diastolic dysfunction of the HCM heart, which is characteristic to HCM. In contrast to sarcomere HCM, the molecular mechanisms underlying the Z-band HCM have not been fully elucidated. However, we previously identified that the HCM-associated TTN mutation Ser3799Tyr increased the binding ability to α-actinin by 40% (12).

The use of the intra-aortic filter device is more invasive and thus may be associated with unfavorable vascular complications such as plaque disruption during deployment and possible aortic perforation.30 Furthermore, the particle filtering cut-off value of the intra-aortic filter device is 120 mm in diameter, while that of the CardioGard

cannula is 72 mm, corresponding to the external filter diameter. This dissimilarity may afford the double lumen cannula better embolus evacuation capacity. A human, multicenter, INK 128 manufacturer randomized, controlled clinical trial is currently under way. Abbreviations AS aortic stenosis; AV aortic valve; AVR aortic valve replacement; BAV balloon Inhibitors,research,lifescience,medical aortic valvuloplasty; CABG coronary artery bypass grafting; CI confidence interval; CPB cardiopulmonary bypass; EuroSCORE European System for Cardiac Operative Inhibitors,research,lifescience,medical Risk Evaluation; LV left ventricle; LVEF left ventricular ejection fraction; MVR mitral valve replacement; NYHA New York Heart Association; OPCAB off-pump coronary artery bypass; OR odds ratio; QOL quality of life; sPAP

systolic pressure in pulmonary artery; STS Society of Thoracic Surgeons; TAVI transcatheter aortic valve implantation. Footnotes Conflict of interest: Dr Bolotin serves as a consultant for CardioGard Inhibitors,research,lifescience,medical Company, the manufacturer of the CardioGard cannula.
The contribution to the Netherlands by the exiled Jewish community of Inhibitors,research,lifescience,medical Iberian origin is well known and was indeed a significant one in the Golden Age of the seventeenth century. It was in this age of reason that an intellectual center evolved in Amsterdam’s Judebeestraat (Jewish street) in the Jewish Quarter (not ghetto), neighboring the beautiful Portuguese Inhibitors,research,lifescience,medical synagogue. It was a center which fostered the development of the arts (by the painter Rembrandt Harmenszoon van Rijn), of Jewish scholarship (by Manasseh ben Israel, a Torah teacher

and publisher of religious books), and of medicine (by members of the Bueno medical dynasty). Rembrandt (1606–1669), the great artist, had settled in the Jewish quarter with his family—his wife and two daughters, and later on his second wife and a son. They GBA3 lived fairly long lives, requiring frequent medical assistance for births, children’s diseases, and adult illnesses. Rembrandt’s interest in Biblical stories is well represented in his many paintings based on the Old Testament (Jewish Wedding, A Young Jew, The Saving of Moses, etc.).1 The painting of Bathsheba with David’s Letter2 depicts a retracted skin deformity on the model’s exposed left breast, a sign of mastitis or perhaps a scirrhous type of carcinoma.3 Toward the end of his life, after his entire family had perished, Rembrandt was unable to satisfy his debtors and was evicted from his home. He died in poverty and was buried in a common grave in Westerkerk cemetery in Amsterdam.